Cardiovascular complications of patients with type 2 diabetes mellitus(T2DM)threaten the health and life of numerous individuals.Recently,growth factor receptor-binding protein 10(GRB10)was found to play a pivotal rol...Cardiovascular complications of patients with type 2 diabetes mellitus(T2DM)threaten the health and life of numerous individuals.Recently,growth factor receptor-binding protein 10(GRB10)was found to play a pivotal role in vascular complications of T2DM,which participates in the regulation of lipid metabolism of T2DM patients.The genetic variation of GRB10 rs1800504 is closely related to the risk of coronary heart disease in patients with T2DM.The development of GRB10 as a key mediator in the association of lipid metabolism with cardiovascular complications in T2DM is detailed in and may provide new potential concerns for the study of cardiovascular complications in T2DM patients.展开更多
BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The...BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform.HCC was used as a search query in GeneCards,Online Mendelian Inheritance in Man,Malacards,DisGeNET,Therapeutic Target Database,and Comparative Toxicogenomics Database.The overlapping targets of the Wuzhuyu decoction and HCC were defined,and then protein-protein interaction,Gene Ontology,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.CytoHubba was used to select hub genes,and their binding activities and key active components were verified using molecular docking.RESULTS A total of 764 compounds,77 active compounds,and 204 potential target genes were identified in Wuzhuyu decoction.For HCC,9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates.A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined,including 10 hub genes(tumor necrosis factor,interleukin-6,AKT1,TP53,caspase-3,mitogen-activated protein kinase 1,epidermal growth factor receptor,MYC,mitogen-activated protein kinase 8,and JUN).There were six main active components(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)that may act on hub genes to treat HCC in Wuzhuyu decoction.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase,p53,phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt,Janus kinase-signal transducer of activators of transcription,and Hippo signaling pathways.Further verification based on molecular docking results showed that the small molecule compounds(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.展开更多
文摘Cardiovascular complications of patients with type 2 diabetes mellitus(T2DM)threaten the health and life of numerous individuals.Recently,growth factor receptor-binding protein 10(GRB10)was found to play a pivotal role in vascular complications of T2DM,which participates in the regulation of lipid metabolism of T2DM patients.The genetic variation of GRB10 rs1800504 is closely related to the risk of coronary heart disease in patients with T2DM.The development of GRB10 as a key mediator in the association of lipid metabolism with cardiovascular complications in T2DM is detailed in and may provide new potential concerns for the study of cardiovascular complications in T2DM patients.
基金Supported by the Xiangshan Talented Scientific Research Project of Zhuhai People’s Hospital,No.2021XSYC-02Research Start Project of Zhuhai People’s Hospital,No.2020ycqd001.
文摘BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform.HCC was used as a search query in GeneCards,Online Mendelian Inheritance in Man,Malacards,DisGeNET,Therapeutic Target Database,and Comparative Toxicogenomics Database.The overlapping targets of the Wuzhuyu decoction and HCC were defined,and then protein-protein interaction,Gene Ontology,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.CytoHubba was used to select hub genes,and their binding activities and key active components were verified using molecular docking.RESULTS A total of 764 compounds,77 active compounds,and 204 potential target genes were identified in Wuzhuyu decoction.For HCC,9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates.A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined,including 10 hub genes(tumor necrosis factor,interleukin-6,AKT1,TP53,caspase-3,mitogen-activated protein kinase 1,epidermal growth factor receptor,MYC,mitogen-activated protein kinase 8,and JUN).There were six main active components(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)that may act on hub genes to treat HCC in Wuzhuyu decoction.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase,p53,phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt,Janus kinase-signal transducer of activators of transcription,and Hippo signaling pathways.Further verification based on molecular docking results showed that the small molecule compounds(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.